Cancer is a leading cause of death worldwide with lung, breast, colorectal, stomach, and prostate cancer causing the majority of deaths. Prostate cancer is the most commonly occurring tumour in males and is second only to lung cancer in mortality. Treatment with surgery and/or radiotherapy is successful in many patients if prostate cancer is diagnosed early. However, many patients with advanced disease and a sizeable proportion of all prostate cancer patients eventually develop metastatic disease following localised therapy.
Antibodies (Abs) are a primary tool in the field of targeted therapy and diagnosis due to their binding specificity/affinity and potential for effector properties upon interaction with their cognate antigens. Increasing numbers of Abs have been approved for medical use and many are under clinical evaluation. Antibodies can be effective diagnostics to identify individuals with a predisposition to diseases such as prostate cancer and/or to diagnose such diseases. In addition, the therapeutic use of some antibodies has been shown to reduce tumour size and extend the survival of afflicted patients.
U.S. Pat. No. 5,622,836 to Walker et al. discloses an antibody named BLCA-38 (BLCA—“bladder cancer”). The document teaches that BLCA-38 is a monoclonal antibody specific for an unknown antigen expressed by bladder carcinoma cells. BLCA-38 is also taught to show specificity for human ovarian and colonic cancer cell lines, as well as some melanoma cell lines, but not to lymphoid (T lymphoid or B lymphoid) and leukemic cell lines.
Subsequently, Russell et al. (2004) (Russell et al., “Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro & in vivo studies”. Cancer Immunol Immunother 2004: 53(5): 411-421) published a study in which BLCA-38 was used to target a cytotoxic peptide to prostate cancer cells. The authors indicate that BLCA-38 is a murine monoclonal antibody raised against the human bladder cancer cell line UCRU-BL-17CL.
A further publication by Russell et al. in 2004 (Russell et al., “Immunohistochemical characterization of the monoclonal antibody, BLCA38, for the detection of prostate cancer”. Cancer Immunol Immunother 2004: 53: 995-1004) also teaches that BLCA-38 is a murine monoclonal antibody raised against a human bladder cell line which is capable of binding to bladder carcinoma cells, prostate cancer cells, and vulval epidermoid cells, but not to breast cancer cells. The article indicates that BLCA-38 is specific for an antigen of approximately 30 kDa in size that is difficult to characterise or identify.
Carter et al. (2004) (Carter et al., “Biodistributions of intact monoclonal antibodies and fragments of BLCA38, a new prostate cancer directed antibody”. Cancer Immunol Immunother 2004: 53:533-542) analysed timing and dosage for targeting therapeutic agents to prostate cancer cells using BLCA-38, also indicating that it is a murine monoclonal antibody targeting an antigen of around 30 kDa expressed on the cell surface and in the cytoplasm. The authors state that the nature of the antigen is elusive, and indicate that it is expressed on bladder and prostate cancer cells.
An article by Khatri et al. published in 2010 (Khatri et al. “Promise of BLCA38 as a Targeting Antibody for Tissue-Specific Gene Delivery to Prostate Cancer”. Austral-Asian J. Cancer 2010: 9(3): 195-203) reiterated that BLCA-38 is a murine monoclonal antibody specific for prostate cancer cells. The authors reveal that although BLCA-38 is not internalised upon binding to its antigen, conjugation with a virus facilitated internalisation of the antibody resulting in increased expression of the reporter gene.
Despite the promise that antibodies offer as diagnostic and therapeutic agents, a need continues to exist for more effective agents to diagnose and/or treat various forms of cancer, including prostate cancer.